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1 The mechanism of cadmium (Cd2+)-induced contraction was studied in isolated ileal longitudinal muscle of guinea-pig. 2 CdCl2 (1x10(-8) to 1x10-4M)) caused a transient contraction which subsided within approximately 6 min of application. The contraction was reproducible and dependent on the concentration. The dose-response curve was bell-shaped. A maximal response was observed at concentrations of 5x10(-6) to 1x10(-5) M. 3 The contractile effect was inhibited to some degree at 20 degree C or by tetrodotoxin (0.1 microgram/ml), hyoscine (o.1 microgram/ml), but completely inhibited by Ca2+ -removal from the medium. 4 Cd2+ increased the output of [14C]-acetylcholine biosynthesized from [14C] by the preparation depending on the concentration. The increase terminated within the first 6 min and was reduced by tetrodotoxin (0.1 microgram/ml) or by removal of Ca2+ from the medium. 5 Both the contractile and transmitter releasing effects of Cd2+ were dependent on the concentration of external Ca2+. Strontium ions were able to replace Ca2+ -induced transmitter release. 6 It is suggested that Cd2+ contracts ileal longitudinal muscle through a release of cholinergic transmitter from the parasympathetic nerve terminals, which is dependent on external Ca2+. It also has a smaller hyoscine-resistant contractile effect, presumably due to a direct action on smooth muscle cells.

Effects of N2-dansyl-L-arginine-4-t-butylpiperidine amide (TI233) on the contractions in vascular and intestinal smooth muscles were examined. High K-induced sustained contractions in the smooth muscles were inhibited by TI233 with an IC50 of 2.1 X 10(-5) M for rabbit aorta and 3.6 X 10(-6) M for guinea-pig taenia coli in a solution containing 1.5 mM Ca. Initial transient contraction induced by K in taenia coli was less sensitive to the inhibitory effect of TI233. When the Ca concentration in the medium was decreased to 0.3 mM, the concentration-inhibition curves for TI233 shifted to the left in both aorta and taenia coli. Increasing the Ca concentration to 7.5 mM shifted the curve to the right in the aorta. TI233 also inhibited the noradrenaline-induced contraction in the aorta (IC50 = 2.1 X 10(-5 M). In a hypoxic solution without added glucose, the inhibitory effect of TI233 on the K-induced contraction in aorta was augmented. In the presence of high concentrations (40 mM) of glucose in hypoxia, TI233 did not inhibit the noradrenaline-induced contraction of the aorta. Hypoxia and a high concentration of glucose also decreased the inhibitory effect of TI233 on the K-induced contraction in taenia coli. TI233 inhibited the K-induced increase in cellular Ca content measured by a modified lanthanum method. TI233 decreased oxygen consumption and ATP content of resting and K-stimulated aorta and taenia coli. It was concluded that TI233 inhibits the vascular and intestinal smooth muscle contraction by a Ca antagonistic action and also by inhibition of aerobic metabolism.